-
BioRxiv : the Preprint Server For... May 2024Mutations in the human Ocular albinism type-1 gene are associated with abnormal retinal pigment epithelium (RPE) melanogenesis and poor binocular vision resulting from...
Mutations in the human Ocular albinism type-1 gene are associated with abnormal retinal pigment epithelium (RPE) melanogenesis and poor binocular vision resulting from misrouting of ipsilateral retinal ganglion cell (iRGC) axons to the brain. We studied the latter using wild-type (WT) and mouse eyes. At embryonic stages, the WT RPE-specific Oa1 protein signals through cAMP/Epac1-Erk2-CREB. Following CREB phosphorylation, a pCREB gradient extends from the RPE to the differentiating retinal amacrine and RGCs. In contrast to WT, the RPE and ventral ciliary-margin-zone, a niche for iRGCs, express less pCREB while their retinas have a disrupted pCREB gradient, indicating Oa1's involvement in pCREB maintenance. retinas also show hyperproliferation, enlarged nuclei, reduced differentiation, and fewer newborn amacrine and RGCs than WT retinas. Our results demonstrate that Oa1's absence leads to reduced binocular vision through a hyperproliferation-associated block in differentiation that impairs neurogenesis. This may affect iRGC axon's routing to the brain.
PubMed: 38798688
DOI: 10.1101/2024.05.14.594013 -
Frontiers in Immunology 2024Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and... (Review)
Review
Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and regulating cellular functions. Vesicle trafficking of lysosomes and LROs are critical to maintain their functions. The lysosomal trafficking regulator (LYST) is an elusive protein important for the regulation of membrane dynamics and intracellular trafficking of lysosomes and LROs. Mutations to the LYST gene result in Chédiak-Higashi syndrome, an autosomal recessive immunodeficiency characterized by defective granule exocytosis, cytotoxicity, etc. Despite eight decades passing since its initial discovery, a comprehensive understanding of LYST's function in cellular biology remains unresolved. Accumulating evidence suggests that dysregulation of LYST function also manifests in other disease states. Here, we review the available literature to consolidate available scientific endeavors in relation to LYST and discuss its relevance for immunomodulatory therapies, regenerative medicine and cancer applications.
Topics: Humans; Lysosomes; Vesicular Transport Proteins; Animals; Chediak-Higashi Syndrome; Protein Transport; Mutation
PubMed: 38774881
DOI: 10.3389/fimmu.2024.1404846 -
Frontiers in Plant Science 2024Proper nutrient management is crucially important to the sustainable development of tea production. Compared to normal green-leaf cultivars, albino tea cultivars produce...
Proper nutrient management is crucially important to the sustainable development of tea production. Compared to normal green-leaf cultivars, albino tea cultivars produce green tea of superior quality characterized by high contents of amino acids as a result of the hydrolysis of chloroplast proteins at albinism. However, the advantage of albino tea cultivars was offset by inferior growth and yield performance because of low contents of chlorophylls and limited photosynthesis capacity. Our understanding about the nutrition characteristics of albino tea cultivars was very limited. A four-year field experiment was conducted to develop proper nutrient management for Baiye-1 to overcome its weakness of low productivity without a tradeoff in tea quality and environmental risks. The nutrient management schemes were formulated by optimizing the rate and ratio of nitrogen (N), phosphorus, potassium and magnesium together with substitution of chemical fertilizers with organic manures. The total amounts of nutrients in the optimized schemes were reduced by 25% compared to the local farmers' practice (FP). Results showed that optimized rates and ratio of nutrients together with partial substitution of chemical fertilizers with rapeseed cake manure more considerably improved albino tea yield, the contents of free amino acids, total polyphenol and catechins relative to FP. Partial substitution of chemical fertilizers with commercial livestock manure decreased tea quality, which was likely caused by a dilution effect of increasing tea yield and decreasing N status of tea plants. Full organic substitution of chemical fertilizers by rapeseed cake manure improved tea yield and quality but had relatively low agronomic efficiency and profit. The effect of optimized nutrient management schemes was associated with the improvement of nutritional status in tea plants. The present work demonstrated that the optimization of nutrient management considerably improved albino tea yield, quality and profit while decreased the application rate of fertilizers and the intensity of greenhouse gas emissions.
PubMed: 38756965
DOI: 10.3389/fpls.2024.1369015 -
American Journal of Ophthalmology Case... Jun 2024To present a case of molecularly confirmed oculocutaneous albinism (OCA) and retinitis pigmentosa (RP).
PURPOSE
To present a case of molecularly confirmed oculocutaneous albinism (OCA) and retinitis pigmentosa (RP).
OBSERVATIONS
A 46-year-old male with a lifelong established diagnosis of OCA and baseline best corrected visual acuity (BCVA) of 20/200, presented for worsening visual acuity over the last few years. BCVA was light perception and hand motion at face for the right and left eye, respectively. Fundus exam showed hypopigmented fundi with visible choroidal vessels and blunted foveal reflexes in both eyes. Optical coherence tomography showed foveal hypoplasia and outer retinal degenerative changes not typical of OCA. Fundus autofluorescence (FAF) imaging showed focal areas of decreased signal at the fovea, similar to areas of atrophy in an age matched patient with -RP. Genetic testing identified a homozygous disease-causing variant in c.1467dup, p. (Ala490Cysfs*20) causing OCA, and a homozygous pathogenic variant c.304C > A, p. (Arg102Ser) in causing autosomal recessive RP.
CONCLUSIONS AND IMPORTANCE
This is the first report of a patient with OCA and RP. The lack of pigmentary changes can make the diagnosis of RP challenging in patients with albinism. FAF can show features suggestive of RP and genetic testing can establish the diagnosis. The findings described herein may help physicians diagnose an extremely rare phenotype.
PubMed: 38745847
DOI: 10.1016/j.ajoc.2024.102068 -
Internal Medicine (Tokyo, Japan) May 2024Herein, we report a case of Hermansky-Pudlak syndrome (HPS) in which respiratory symptoms improved with pirfenidone treatment. A 43-year-old Japanese woman with...
Herein, we report a case of Hermansky-Pudlak syndrome (HPS) in which respiratory symptoms improved with pirfenidone treatment. A 43-year-old Japanese woman with oculocutaneous albinism presented with a cough and dyspnea. High-resolution computed tomography revealed areas of reticular and frosted lung opacities. The diagnosis of HPS was confirmed by a prolonged bleeding time and HPS1 gene mutation. Generally, there is no effective treatment for interstitial pneumonia associated with HPS except for lung transplantation. In the present case, the cough and dyspnea improved with pirfenidone administration. Therefore, clinicians should administer pirfenidone in challenging transplantation cases and during the waiting period for transplantation.
PubMed: 38719600
DOI: 10.2169/internalmedicine.3459-24 -
Cancers Apr 2024We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi. What have we learned?
BACKGROUND
We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi. What have we learned?
METHODS
Three surgical campaigns were performed in Nkhotakota district (2019-2023). Albino clinical and tumor characteristics were collected.
RESULTS
Between 22 and 75 albinos were evaluated in each campaign (mean age < 28 years old). Most patients did not use sunscreen in a way that provided optimal photoprotection. Regarding tumors, the proportion of basal and squamous cell carcinomas ranged from 1:1 to almost 2:1. Of 156 albino patients, 34 attended more than once. However, of the 19 patients with 30 tumors operated on in 2021, only seven were assessed the following year (12 were lost to follow-up). At least 14 albinos with locally advanced tumors were evaluated.
CONCLUSIONS
Distributing photoprotective clothing could be more efficient or perhaps an earlier measure of sunscreen in rural Africa as it does not require permanent repositioning. Very-high-risk patients (previous interventions with positive margins or high-risk tumors, intense actinic damage, and new tumors constantly appearing, especially those presenting SCCs) require close follow-up and treatment and represent our main target. Secondary prevention with Malawian collaboration and the use of teledermatology is essential for patient tracking, as they are able to offer curative treatments.
PubMed: 38672604
DOI: 10.3390/cancers16081522 -
Arquivos Brasileiros de Oftalmologia 2024We present a case report detailing the successful phacoemulsification surgery with artificial iris implantation for two individuals with oculocutaneous albinism. These...
We present a case report detailing the successful phacoemulsification surgery with artificial iris implantation for two individuals with oculocutaneous albinism. These women suffered from cataracts, resulting in reduced visual acuity and heightened photophobia due to iris pigmentary epithelium deficiency. The patients underwent phacoemulsification along with prosthetic artificial iris implantation into the posterior chamber. This intervention resulted in improved visual acuity, reduced photophobia and glare, and an overall enhanced quality of life. Our report highlights two cases of successful phacoemulsification and artificial iris implantation in patients with oculocutaneous albinism and cataracts, leading to improved visual acuity, reduced photophobia, and enhanced quality of life. Notably, there are no prior records in South American literature of cataract surgery combined with artificial iris implantation for oculocutaneous albinism patients up to the time of this publication.
Topics: Humans; Albinism, Oculocutaneous; Female; Visual Acuity; Iris; Phacoemulsification; Treatment Outcome; Cataract; Quality of Life; Adult; Artificial Organs; Prosthesis Implantation; Middle Aged; Photophobia
PubMed: 38656019
DOI: 10.5935/0004-2749.2022-0286 -
Scientific Reports Apr 2024Crowding is a phenomenon in which the ability to recognize an object in a clutter deteriorates. It is, therefore, a fundamental aspect of object recognition and crucial...
Crowding is a phenomenon in which the ability to recognize an object in a clutter deteriorates. It is, therefore, a fundamental aspect of object recognition and crucial in deciphering resolution. For visually impaired individuals, deficiency in crowding has a tremendous effect on vision and may reflect and predict the amount of deterioration in vision. It is well established that albinos suffer much more from crowding than normally sighted individuals under daylight luminance conditions. However, to our knowledge, this study is the first to investigate crowding in albino participants under low light conditions. In this study, we explored the crowding effect in a group of albino participants (n = 9) and a control group of normally sighted participants (n = 9). Crowding was conducted under daylight (photopic vision) and low light (scotopic vision). We measured the visual acuity threshold under crowding in three-letter spacing (0.5, 1, and 1.5) and compared it to a single target. Results indicate that albino participants experienced stronger crowding than the control under the photopic condition, while crowding under the scotopic condition was apparent in the albino but abolished for the control group. These findings highlight the importance of considering luminance when discussing the visually impaired population in general. In particular, it suggests that crowding in albinism is based on a peripheral-like mechanism and may indicate a cessation in visual development.
Topics: Humans; Color Vision; Visual Perception; Visual Acuity; Visually Impaired Persons; Crowding; Albinism
PubMed: 38589506
DOI: 10.1038/s41598-024-58369-0 -
Investigative Ophthalmology & Visual... Apr 2024Our primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate...
PURPOSE
Our primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate the effect of within-subject changes in nystagmus eye movements on ffERG responses.
METHODS
Dilated Ganzfeld flash ffERG responses were recorded using DTL electrodes under conditions of dark (standard and dim flash) and light adaptation in 68 participants with albinism, 43 with IIN, and 24 controls. For the primary aim, the effect of group and age on ffERG responses was investigated. For the secondary aim, null region characteristics were determined using eye movements recorded prior to ffERG recordings. ffERG responses were recorded near and away from the null regions of 18 participants also measuring the success rate of recordings.
RESULTS
For the primary aim, age-adjusted photopic a- and b-wave amplitudes were consistently smaller in IIN compared with controls (P < 0.0001), with responses in both groups decreasing with age. In contrast, photopic a-wave amplitudes increased with age in albinism (P = 0.0035). For the secondary aim, more intense nystagmus significantly reduced the success rate of measurable responses. Within-subject changes in nystagmus intensity generated small, borderline significant differences in photopic b-wave peak times and a-and b-wave amplitudes under scotopic conditions with standard flash.
CONCLUSIONS
Age-adjusted photopic ffERG responses are significantly reduced in IIN adding to the growing body of evidence of retinal abnormalities in IIN. Differences between photopic responses in albinism and controls depend on age. Success at obtaining ffERG responses could be improved by recording responses at the null region.
Topics: Adult; Humans; Nystagmus, Congenital; Nystagmus, Pathologic; Eye Movements; Albinism; Genetic Diseases, X-Linked
PubMed: 38573619
DOI: 10.1167/iovs.65.4.11 -
Scientific Reports Mar 2024The purpose of this paper is to expand on the phenotype of oculocutaneous albinism type 7 (OCA7). We described three patients with OCA7: two from a consanguineous family...
The purpose of this paper is to expand on the phenotype of oculocutaneous albinism type 7 (OCA7). We described three patients with OCA7: two from a consanguineous family of Kurdish origin and one patient of Dutch origin. We compared them with all patients described to date in the literature. All newly described patients had severely reduced visual acuity (VA), nystagmus, hypopigmentation of the fundus, severe foveal hypoplasia, and chiasmal misrouting. None had iris translucency. All patients had normal pigmentation of skin and hair. We found one novel mutation in the Dutch patient: c.565G > A; p.(Gly189Ser). We compared our patients to the 15 described in the literature to date. All 18 patients had substantially pigmented skin and hair, very poor VA (0.4-1.3 logMAR), nystagmus, (mild) ocular hypopigmentation, foveal hypoplasia, and misrouting. Although pigmentation levels were mildly affected in OCA7, patients had a severe ocular phenotype with VA at the poorer end of the albinism spectrum, severe foveal hypoplasia, and chiasmal misrouting. OCA7 patients had a phenotype restricted to the eyes, and similar to that of X-linked ocular albinism. We therefore propose to rename the disorder in ocular albinism type 2. Unfolding the role of LRMDA in OCA7, may bring us a step closer in identifying the responsible factors for the co-occurrence of foveal hypoplasia and misrouting.
Topics: Humans; Albinism, Ocular; Albinism, Oculocutaneous; Nystagmus, Pathologic; Hypopigmentation; Retina; Mutation; Vision Disorders
PubMed: 38555393
DOI: 10.1038/s41598-024-57969-0